Fitzakerly: Anti-ulcer Drugs Flashcards
What diseases are treated w/ anti-ulcer drugs?
- Peptic acid disease (H. Pylori, NSAIDS)
- GERD and NER
- Hypersecretory States (hyperacidity, dyspepsia, stress ulcers, gastrinoma, systemic mastocytoses)
What are the objectives for treating PUD, hypersecretory diseases and GERD?
- Heal the lesion
- Stop the pain
- remove possibility of recurrence
- avoid complications
- eliminate maintenance doses
- prevent development of resistance
What are the treatment strategies?
- eliminate the cause (h. pyolori)
- Reduce pain by decreasing H secretion
- Eliminate NSAIDs
What are hte most effective drugs for preventing and treating peptic ulcer disease? Why?
Antimicrobials because they ERADICATE H. pylori
Amoxicillin clarithromycin metronidazole rifabutin tetracycline
What is the penicillin of choice for h. pylori? Why?
Amoxicillin
More acid stable
More than twice the blood levels are achieved w/ the same oral dose
Affective against gram -
What is the MOA and toxicity of Amoxicillin?
CIDAL
cell wall inhibitors
hypersensitivity
What is the macrolide antibiotic of choice for h. pylori treatment?
Clarithromycin
Why is clarithromycin better than azithro or erythro?
lowest MIC50 and is more acid stable
How do you compare azithro, clarithro and erythro?
Azithro and clarithro are better than erythro b/c they can be given at lower doses and have less GI effects.
Clarithro is better than azithro b/c the MIC90 is .06 vs. .25
What is the MOA of macrolides? Toxicity?
Static
Protein synthesis inhibitor (50S RNA)
GI irritation
drug interactions
What else can be used to treat h. pylori infections? Co administration with what can significantly decrease the antibiotic efficacy d/t chelation.
Tetracyclines
Antacids
You should always give tetracycline w/ ______NOT ________.
Food
NOT antacids
What is the MOA and toxicity of tetracyclines?
Static
protein synthesis inhibitors (30S)
Gi irritation
photosensitivity
discoloration of teeth (not good for pregnant women or children)
What drug is a bacterialcidal and inhibits hte DNA dep RNA pol?
Rifabutin= rifamycin
What are the SE of rifamycin?
Hypersensitivity/fever
hepatotoxicity
cyp 450 inhibition
orange/red body fluids
Why don’t we often use metronidazole/tinidazole to treat h. pylori?
up to 65% of infections are resistant
What is the MOA and SE of metronidazole/tinidazole?
DNA damage?
SE: GI, CNS toxicity, disulfiram rxn, teratogenic
Inhibits cyp2C9 (can potentiate warfarin and reduce clearance of H2 blockers)
What is the MOA of Bismuth?
- Antimicrobial- disrupts the cell wal and prevents adhesion or inhibits urease
- protects surface (coats surface and stimulates secretion of mucus, PG and bicarb)
Bismuth is only active in ______not_______.
stomach not the lower GI
Whare are the SE of bismuth subsalicylate?
Subsalicylate causes most SE: vomiting, tinnitus, confusion, hyperthermia, resp. alkalosis> met. acidosis
Bismuth: black tongue/stool
What are the causes of antimicrobial treatment failure?
- resistance (metronidazole and clarithromyacin)
2. compliance (too many pills for too long)
What drugs are used to eradicate H. Pylori?
- Amoxicillin
- Clarithromycin
- Tetracycline
- Rifabutin
- Metronidazole/tinidazole
- Bismuth subsalicylate
What drugs promote mucosal defence?
- bismuth subsalicylate
- misoprostol
- simethicone
- sucralfate
What antacids reduce intragastric acidity?
- aluminum hydroxid
- Ca carbonate
- magnesium hydroxide
- sodium bicarbonate
What antimuscarinics reduce intragastric acidity?
- atropine
2. pirenzipine
What H1 blockers reduce intragastric acidity?
- Cimetidine
- famotidine
- Nizatidine
- Ranitidine
- roxatidine
What PPI reduce intragasric acidity?
- lansoprazole
- omeprazole and esomeprazole
- pantoprazole
- raberprazole
What drugs are RARELY used to treat ulcers b/c they slow gastric emptying and prolong exposure of the ulcer to acid?
Muscarinic receptor ANTAGONISTS
Atropine
pirenzipine
*also have a more severe SE htan H2 blockers
How does ACh trigger acid secretion?
ACh acts on M1 (ECL) and M3 (Parietal cell) leading to acid secretion
What type of receptors are muscarinic receptors?
M1 and M3>
G protein linked>
activate phospholipiase C and D>
increase in IP3
What is the MOA of atropine and pirenzipine?
compeptive inhibitors of ACh
Which muscarinic receptor antagonist is M1 selective?
pirenzipine
What are the SE of atropine and pirenzipine?
ABCD'S Anorexia blurry vision constipation/confusion dry mouth sedation/stasis of urine
What drugs are NOT used to tx ulcers?
Muscarinic receptor antagonists
Overdose of atropine will cause…
CNS: hallucinations/ confusion
tachycardia
hot, dry skin
What drugs are H2 receptor antagonists?
CIMETIDINE
famotidine
nizatidine
ranitidine
What do H2 receptor antagonists do?
Decrease ALL forms of gastric acid secretion (esp nocturnal)
Why are H2 receptor antagonists OTC?
they ahve few SE except cimetidine and can be given orally
What is the primary effect of H2RAs?
They are competitive antagonists of H2 and are highly selective (no H1 activity)
What is the secondary effect of H2 receptor antagonists?
Decrease intracellular cAMP> basal and nocturnal secretion d/t other agents
What is the t1/2 of H2RA?
Usually 1-4 hrs but they have extensive hepatic metabolism and are excreted renally
Which H2RA is hte best tolerated?
Famotidine (highest potency + smallest dose)
What are the SE of H2RA?
No SE when given ORALLY to HEALTHY pt
Why is it bad to give a pt rapid IV infusion of H2RA?
bradycardia and hypotension
*there are H2 receptors in the heart so you have to give a slow infusion
What drug drug interactions are seen with H2RA?
- decreased ethanol metabolism (esp in women)
2. Compete for tubular secretion w/ weak bases (metronidazole)
High doses of Cimetidine can cause…
- decrease binding of DHT to androgen receptors
decreased estrogen metabolism
incerased prolactin–>
gynecomastia and impotence in men
galactorrhea in women
- inhibition of cyp450 (increases effectiveness of other drugs)
Which drug has a therapeutic advanatage esomeprazole or omeprazole?
Esomeprazole is exclusively the S isomer (omeprazole is the racemic mixture) and is metabolized more slowly and reproducibly
What are the most effective agents for reducing intragastric acidity b/c they IRREVERSIBLY block the final common pathway in acid secretion—the H/K ATPase in the parietal cell?
PPI: esomeprazole/omeprazole lansoprazole pantoprazole rabeprazole
What drugs are good for treating GERD and ZE syndrome?
PPI
Why do PPIs need a coating?
they are prodrugs that become labile in acid and must pass through the stomach to be absorbed
Where are PPIs absorbed/concentrated?
SI then circulate throughout the body>
concentrate in teh acidified compartments>
protonated>
active form
What should you give a PPI?
give drug 1/2 hr before meal so the concentration is highest when the pumps are active
What are the SE of PPIs?
No sig SE
Some pts may experience HA, diarrhea, nausea, rash
What is the danger of stopping PPIs in a pt who has been using them for a long time?
rebound acid hypersecretion
What concerns are associated w/ long term use of PPIs?
- Decreased B12, FE, Ca, Zinc absorption> hip fx
- increased respiratory and enteric infections (increased pH)
- ECL hyperplasia (hypergasrinemia)
Normally a decreased gastric pH> increases SS release> and leads to a decrease in gastrin
What is used to buffer stomach acid?
Weak bases: Aluminum hydroxide Ca carbonate Mg hydroxide Na Bicarbonate
What weak bases are systemically absorbed?
NaHCO3 the most
CaCO2 some
What drugs have a fast rate of dissociation?
NaHCO2 and CaCO2
What weak bases create gas and can cause belching?
CaCO2 and NaHCO3
aluminum hydroxide
Efficient and low systemic absorption
CONSTIPATION (not effective when given alone)
Decreases PO4 absorption> increased Ca loss> osteomalacia
magnesium hydroxide
Efficient and low systemic absorption (like Al
OSMOTIC DIARRHEA
Renal insufficiency> hypermagnesemia> CNS and cardiotoxicity
Calcium carbonate
Rapid onset of action and long duration
Belching/gastric distention, rebound acid secretion
MILD SYSTEMIC ALKALOSIS
Na Bicarbonate
Extremely RAPID onset of action
bleching, gastric distention, short duration of action
SEVERE METABOLIC ALKALOSIS
ALKALINIZES URINE
What drug interactions are associated w/ weak bases?
- increase gastric pH (can increase or decrease absorption)
- binds drugs (decrease absorption)
- increases gastric emptying (decreased absorption)
- systemic absorption (alkalinize urine)
What is simethicone?
antifoaming agent that decreases gas pain
*also affects absorption
What is the difference between antacids, H2 blockers and PPIs?
Antacids: rapid onset, short duration, INTERMITTENT DYSPEPSIA (don’t prevent ulcer recurrence)
H2 blockers: rpaid onset, intm duration, some prevention
PPI: slow onset, ong duration, EXCELLENT prevention
What is the drug of choice for ZE syndrome, GERD and ulcer treatment?
PPIs
What is sucralfate?
Al (OH3) and sulphated sucrose (NOT an antacid)
What is the MOA of sucralfate?
attaches to ulcer surface (acts like a band aid)
Sucralfate is used to tx?
stress induced ulcers in the ICU
What does sucralfate require and what should it not be taken with?
acidic environment to be converted to paste
interacts w/ PPI and H2 blocker
What are the SE of sucralfate?
constipation
binds other drugs
What does misoprostol do?
replaces prostaglandins
What percent of ulcers are caused by NSAIDs?
5%
Why does misoprostol owrk?
PGE is less involved w/ inlammation and misoprostol t1/2 is 30-40 min compared to acetaminophen and ibuprofen (2hrs)
What are the pharmikokinetics of misoprostol?
rapid absorption and metabolism
excreted in urine
What are the SE of misoprostol?
diarrhea, severe nausea, cramping, abdominal pain
What drug can also be used as an aborficant b/c it stimulates uterine contractions?
MIsoprostol
What is triple therapy?
PPI + )clarithryomyacin for 5 days followed by amoxicillin or tinidazole for 5 days)
What is quadruple therapy?
PPI + tetracycline + metornidazole + bismuch subsalicylate for 14 days
What is a last choice therapy for ulcers?
PPI+ amoxicillin + rifabutin + cipro for 10 days
At a low pH will you get more gastric absorption of WA or WB?
More of WA
At a high pH will you get more gastric absorption of WA or WB?
WB will increase (PPI, H2 blocker, antacid)
At a low pH will you get more excretion of WA or WB?
MOre WB
At a high pH will you get more excretion of WA or WB?
More WA (antacids)
